Aggregator

Complex biological features such as the human microbiome and gene expressions play a crucial role in human health by mediating various biomedical processes that influence disease progression, such as immune responses and metabolic processes. Understanding these mediation roles is essential for gaining insights into disease pathogenesis and improving treatment outcomes. However, analyzing such high-dimensional mediation features presents challenges due to their inherent structural and...

Amylin, also known as islet amyloid polypeptide (IAPP), is a pancreatic β-cell peptide hormone involved in satiation and control food intake. It is also produced in smaller quantities by neurons, the gastrointestinal tract, and spinal ganglia. Numerous studies have revealed that patients with type 2 diabetes mellitus (T2DM) and cognitive deficits exhibit IAPP deposits in the pancreas, brain, and blood vessels. IAPP has also been shown to exert neuroprotective effects against Alzheimer's disease...

Tissue-regulated alternative exons are dictated by the interplay between cis-elements and trans-regulatory factors such as RNA binding proteins. Despite extensive research on splicing regulation, the full repertoire of these cis and trans features and their evolutionary dynamics across species are yet to be fully characterized. Members of the CUG-binding protein and ETR-like family (CELF) of RNA binding proteins are known to play a key role in the regulation of tissue-biased splicing patterns,...

The recent surge of large language models has shown that machines are capable of reading, understanding, and communicating through language, even sometimes displaying capabilities surpassing those of humans. Proteins can be represented as strings of amino acids akin to words in a sentence, and the same principles of language modeling can be used to learn informative representations for protein structure prediction, design, and property prediction. In this review, we will focus on applications of...

CONCLUSIONS: Among individuals with antenatal depression, ICBT did not prevent the development of PPD. However, ICBT may be a preferable option for those with mild to moderate antenatal depressive symptoms. Future research is needed to explore modifications to ICBT to address more severe depressive symptoms.

Intestinal protists are detected by the host innate immune system through mechanisms that remain poorly understood. Here, we demonstrate that Tritrichomonas protozoa induce thickening of the colonic mucus in an NLRP6-, ASC-, and caspase-11-dependent manner, consistent with the activation of sentinel goblet cells. Mucus growth is recapitulated with cecal extracts from Tritrichomonas-infected mice but not purified protozoa, suggesting that NLRP6 may detect infection-induced microbial dysbiosis. In...

Many regulatory factors impact the expression of individual genes including, but not limited, to microRNA, long non-coding RNA (lncRNA), transcription factors (TFs), cis-methylation, copy number variation (CNV), and single-nucleotide polymorphisms (SNPs). While each mechanism can influence gene expression substantially, the relative importance of each mechanism at the level of individual genes and tissues is poorly understood. Here, we present the integrative Models of Estimated gene expression...

MYC-driven (MYC+) cancers are aggressive and often fatal. MYC dysregulation is a key event in these cancers, but overexpression of MYC alone is not always enough to cause cancer. Plasmocytoma Variant Translocation 1 (PVT1), a long non-coding RNA (lncRNA) adjacent to MYC on chromosome 8 is a rearrangement hotspot in many MYC+ cancers. In addition to being co-amplified with MYC, the genomic rearrangement at PVT1 involves translocation, which has had obscure functional consequences. We report that...

Psoriasis and spondyloarthritis (SpA), including psoriatic arthritis (PsA), are immune-mediated inflammatory conditions that affect the skin and musculoskeletal system. Males and female patients with psoriatic disease and SpA exhibit differences in clinical presentation, disease progression, and treatment response. The underlying biological mechanisms driving these sex differences remain poorly understood. This review explores the current evidence on sex-related differences in biomarkers and...

Diet, microbiome, inflammation and host genetics have been linked to colorectal cancer development; however, it is not clear whether and how these factors interact to promote carcinogenesis. Here we used Il10^(-/-) mice colonized with bacteria previously associated with colorectal cancer: enterotoxigenic Bacteroides fragilis, Helicobacter hepaticus or colibactin-producing (polyketide synthase-positive (pks^(+))) Escherichia coli and fed either a low-carbohydrate (LC) diet deficient in soluble...

Plants are essential for human survival. Over the past three decades, work with the reference plant Arabidopsis thaliana has significantly advanced plant biology research. One key event was the sequencing of its genome 25 years ago, which fostered many subsequent research technologies and datasets. Arabidopsis has been instrumental in elucidating plant-specific aspects of biology, developing research tools, and translating findings to crop improvement. It not only serves as a model for...

Liquid-liquid phase separation (LLPS) involving intrinsically disordered protein regions (IDRs) is a major physical mechanism for biological membraneless compartmentalization. The multifaceted electrostatic effects in these biomolecular condensates are exemplified here by experimental and theoretical investigations of the different salt- and ATP-dependent LLPSs of an IDR of messenger RNA-regulating protein Caprin1 and its phosphorylated variant pY-Caprin1, exhibiting, for example, reentrant...

Spatial variations of atmospheric alkylated polycyclic aromatic hydrocarbons (Alk-PAHs) are key to understanding their long-range atmospheric transport (LRAT). However, limited Alk-PAHs data have hindered their LRAT characterizations on a global scale. In this study, 49 Alk-PAHs were measured in the atmospheric samples collected across the Western Pacific to the Southern Ocean. The summed concentration of 39 frequently detected Alk-PAHs (Σ(39)Alk-PAHs) was 25.8 ± 25.3 ng m^(-3). The...

For genetic association analysis based on multiple SNP regression of genotypes obtained by dense DNA sequencing or array data imputation, multi-collinearity can be a severe issue causing failure to fit the regression model. In this study, we propose a method of Dimension Reduction using Local Principal Components (DRLPC) which aims to resolve multi-collinearity by removing SNPs under the assumption that the remaining SNPs can capture the effect of a removed SNP due to high linear dependency....

This Letter presents a search for highly ionizing magnetic monopoles in 262 μb^{-1} of ultraperipheral Pb+Pb collision data at sqrt[s_{NN}]=5.36 TeV collected by the ATLAS detector at the LHC. A new methodology that exploits the properties of clusters of hits reconstructed in the innermost silicon detector layers is introduced to study highly ionizing particles in heavy-ion data. No significant excess above the background, which is estimated using a data-driven technique, is observed. Using a...

Psoriasis is a common, debilitating immune-mediated skin disease. Genetic studies have identified biological mechanisms of psoriasis risk, including those targeted by effective therapies. However, the genetic liability to psoriasis is not fully explained by variation at robustly identified risk loci. To refine the genetic map of psoriasis susceptibility we meta-analysed 18 GWAS comprising 36,466 cases and 458,078 controls and identified 109 distinct psoriasis susceptibility loci, including 46...

The increasing presence of antibiotics in urban wastewater has raised significant concerns. Therefore, wastewater treatment plants (WWTPs) face questions about their ability to reliably and effectively remove antibiotics. In this study, data from ten representative WWTPs were systematically evaluated to assess antibiotic occurrence, removal efficiencies, seasonal variations, and ecological risks, revealing the prevalent instability in antibiotic removal capacities of traditional WWTPs. The...

Advances in genomic technologies have revolutionized the diagnosis of rare genetic diseases, leading to the emergence of precision therapies. However, there remains significant effort ahead to ensure the promise of precision medicine translates to improved outcomes. Here, we discuss the challenges in advancing precision child health and highlight how international collaborations such as the International Precision Child Health Partnership, which embed research into clinical care, can maximize...

No abstract

Background: The Safety and Immunogenicity of COVID-19 Vaccines in Systemic Autoimmune-Mediated Inflammatory Diseases (SUCCEED) study was created to better understand COVID-19 vaccination in immune-mediated inflammatory disease (IMID). Knowing the frequency of COVID-19 breakthrough infections is important, particularly in IMID. Our objective was to assess these events in IMID. Methods: We prospectively studied IMID participants who had received ≥three COVID-19 vaccine doses. Individuals provided...